Cartilage is a highly specialized connective tissue with distinct morphological and biochemical characteristics. It contains an extensive extracellular matrix and provides mechanical strength to resist compression in joints. In development, cartilage serves as the template for the growth and development of most bones. When cartilage formation is impaired, skeletal malformation of the limbs, craniofacial bones, and appendicular skeleton occurs. Chondrocytes produce large amounts of cartilage-specific matrix molecules, including type II collagen, aggrecan, link protein, and hyaluronan. Cartilage development is initiated by mesenchymal cell condensation to form primordial cartilage followed by chondrocyte maturation. These include resting, proliferative, prehypertrophic, and hypertrophic chondrocytes. As a final step in endochondral bone formation, hypertrophic cartilage is invaded by blood vessels and osteoprogenitor cells, and the calcified cartilage is subsequently replaced by bone. Thus, spatial and temporal regulation of chondrocyte differentiation is essential in determining the length and width of skeletal components. Hormones and vitamins affect cartilage development and maturation by regulating the transcription of genes. Our objective is to define the mechanisms for activating chondrocyte-specific genes and to elucidate the molecular basis of cartilage development. Using an animal model, we also study the function of cartilage proteins in vivo. We initiated the Oral and Craniofacial Genome Anatomy Project (OC-GAP) to identify novel genes important for tooth and craniofacial development. Our goal is to discover and characterize previously unknown genes to help understand how tooth and craniofacial tissues develop and to define the molecular defects underlying anomalies of these tissues or oral cancer. Craniofacial anomalies of the mouth, neck, and head are of major public concern. A large number of genes are involved in such anomalies and cancers. We have started to identify and catalogue the genes involved in specific stages of tooth and craniofacial development. The identification of genes that have highly location- and stage-specific expression is important since the gene products are likely to have key roles in the formation of craniofacial tissues. It is also expected that mutations in these genes cause anomalies. This information will also be useful for generating diagnostic reagents, developing methods for disease and birth defect prevention, and for potential gene therapies.